Oligodendrocytic protein contribute to neuronal accumulation of alpha-synuclein in multiple system atrophy

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830045
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center (2014); National Center for Geriatrics and Gerontology (2013)
• Principal Investigator: SUZUKI Yasuyo 愛知県心身障害者コロニー発達障害研究所, 遺伝学部, 研究員 (60416188)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: α-synuclein / 神経変性疾患 / 多系統萎縮症

Outline of Final Research Achievements

Multiple system atrophy (MSA) is a neurodegenerative disease in which oligodendrocytes and neurons in the central nervous system are affected. To clarify how oligodendrocytic α-synuclein inclusions cause neuronal degeneration, we generated a transgenic mouse for an MSA model in which human wild-type α-synuclein was overexpressed selectively in oligodendrocytes. We established primary culture cells derived from the brain of transgenic mice, and revealed that insoluble mouse α-synuclein was progressively accumulated in neurons, leading to neuronal dysfunction and degeneration. In this study, we identified cystatin C as a neurodegeneration-inducing factor released from oligodendrocytes. Cystatin C triggers insoluble α-synuclein accumulation in neurons of the mouse central nervous system.

Free Research Field

生化学